Regulatory T cells (Tregs) are recognized as an important immunomodulatory component of the adaptive immune system. Immune dysregulation may lead to chronic inflammation, triggering chronic insulin insensitivity and non-alcoholic steatohepatitis (NASH). The role of Tregs in the adipose tissue in the regulation of NASH was not previously studied. Aim: To assess the effects of Tregs stimulation on hepatic injury and insulin resistance in NASH. Methods: Leptin deficient Ob/Ob mice were fed for 4 weeks with colostrum derived solutions (CDS) enriched with anti insulin specific antibodies (AIS-CDS, Immuron, Australia), or with purified anti insulin specific CDS (PAIS-CDS). The immunologic effect on the adipose tissue was determined by flow cytometry performed on the central adipose tissue and its stromal vasculature (SV), and compared with the effect on immune system of the liver and the spleen. Hepatic injury and insulin resistance was determined by glucose tolerance tests (GTT) and liver enzymes. Results: Oral administration of anti-insulin antibodies promoted the SV CD4+CD25+FoxP3+ cells (13.05 vs. 27.94 p=0.01). Treatment was associated with a decrease of the CD4+IL17+ lymphocyte subset in the adipose tissue (87.89 vs. 12.93, p<0.01), the SV (61.86 vs. 14.99, p<0.01), and in the liver (40.18 vs. 2.66, p<0.01). The liver CD8+CD25+FoxP3+ lymphocyte subset was significantly increased (0.36 vs. 2.39, p<0.05). The CD4/CD8+ lymphocyte ratio in the adipose tissue showed a mirror effect to that of the spleen and liver suggesting an opposite effect on lymphocyte trapping. Promotion Tregs in the adipose tissue was accompanied by a marked improvement in insulin resistance manifested by decreased glucose and insulin serum levels, and improved glucose tolerance test results (a decrease of 45%, in the area under the curve 23355 vs. 42448, in treated vs. controls, respectively), along with decreased liver enzymes (ALT levels decreased from 743.4 to 379.8 IU, p<0.05; and AST from 770.5 to 299IU, in controls vs., treated respectively, p=0.07) without a change in body weight. Conclusions: The immune system of the adipose tissue plays an important role in the regulation of the metabolic syndrome. Decreasing TH17 in the liver, adipose tissue and SV, along with promotion of CD4+CD25+FoxP3+ and CD8+CD25+FoxP3+ Tregs (in the SC and liver respectively), by oral administration of anti insulin CDS offers a new treatment modality for NASH and insulin resistance, making Tregs in adipose tissue as a new therapeutic target for alleviation of the liver damage in NASH.